We propose to examine inner ear development using zebra fish, Danio rerio, as a model system. Zebra fish has emerged as a powerful experimental organism because of the ease of use in developmental biology and genetic studies. The zebra fish inner ear is essentially the same as that in other vertebrates: a closed epithelial structure with three communicating chambers and three semicircular canals. However, no cochlea or cochlear duct is found in the fish ear. Sensory patches are found within the chambers and canals, composed of hair cells and supporting cells. Hair cells synapse with statoacoustic ganglion (SAG) cells that relay the signals to the brain. Otoliths in the matrix above the sensory patches allow teleost fish to detect mechanical stimulation, including linear and rotational acceleration, gravity and sound. Cadherin cell adhesion molecules control a variety of developmental processes, including processes like cell sorting, differentiation and neurite formation in the nervous system. We propose to determine the role of cadherin cell adhesion molecules during the development of the inner ear and SAG. Three specific aims will be employed; (1) determine expression pattems of cadherins in the inner ear of developing zebra fish; (2) determine the function of cadherins during inner ear development; and (3) determine the effects of Pax-2 gene function on cadherin expression during otic placode induction, inner ear development and statoacoustic ganglion (SAG) formation.